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During orthodontic treatment, application of forces to move the teeth within the dento-alveolar complex is associated with structural and biological tissues changes. One of the main changes is hypoxia which is due to the compression of blood vessels resulting in insufficient oxygenation of the tissues. On orthodontic loading, hypoxia causes irreversible cell cycle arrest (or so called cellular senescence) and apoptosis of the tissue cells around the teeth especially on the compression zone. Excessive hypoxia, in turn leads to a massive, an inevitable and detrimental destruction of tissues supporting the tooth such as remarkable root resorption. This mini-review is highlighting the effect of orthodontic force in inducing a local hypoxic environment and its consequences in causing cells death of the periodontal cells.